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Videos

1 expert is featured in this series.

RATIONALE-305: Efficacy, Safety, and Real-World Applicability of Tislelizumab + Chemotherapy in Gastric/GEJ Adenocarcinoma

ByDavid H. Ilson, MD, PhD,Fadi Braiteh, MD ,Jun Gong, MD

This discussion provides a focused summary of the RATIONALE-305 trial, which evaluated tislelizumab in combination with platinum-based chemotherapy as first-line treatment for patients with previously untreated, HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma. The discussion highlights the global, randomized design of the study and its key finding: adding tislelizumab to chemotherapy produced a statistically significant improvement in overall survival compared with chemotherapy alone. The benefit was observed in the intent-to-treat population and was greater in tumors expressing PD-L1 based on the trial’s predefined TAP scoring. Experts also note that the safety profile of the tislelizumab regimen was manageable and consistent with expectations for PD-1 inhibitors plus chemotherapy, with no new or unexpected toxicities reported. Overall, the segment underscores how the results of RATIONALE-305 support the role of tislelizumab-based therapy as an important emerging option in first-line treatment of advanced gastric or GEJ adenocarcinoma.

1 expert is featured in this series.

Mechanism of Action & Potential Impact of Tislelizumab

ByDavid H. Ilson, MD, PhD,Fadi Braiteh, MD ,Jun Gong, MD

This discussion explores how tislelizumab’s unique Fc-region engineering may influence its activity in gastric cancer, particularly in patients with peritoneal metastases. Tislelizumab is designed to minimize binding to Fc-gamma receptors on macrophages, a modification intended to reduce macrophage-mediated clearance of activated T cells and help support a sustained anti-tumor immune response. This mechanism is scientifically relevant in the peritoneal cavity, where macrophages are abundant and can contribute to an immunosuppressive microenvironment. By limiting interaction with these cells, tislelizumab may offer a theoretical advantage in this difficult-to-treat subgroup. While this rationale is grounded in mechanistic biology, clinical validation is still needed to determine the extent of benefit in patients with peritoneal metastases. This segment highlights the scientific foundation behind tislelizumab’s design and its potential implications for addressing unmet needs in advanced gastric cancer.

1 expert is featured in this series.

Current Treatment Standards and Ongoing Challenges in Gastric Cancer

ByDavid H. Ilson, MD, PhD,Fadi Braiteh, MD ,Jun Gong, MD

This discussion provides a clear overview of current treatment standards and ongoing challenges in the management of advanced gastric cancer. The discussion outlines how first-line therapy is anchored in HER2 status: patients with HER2-positive tumors receive HER2-targeted therapy combined with chemotherapy, while those with HER2-negative disease are treated with a PD-1 inhibitor plus platinum-based chemotherapy. PD-L1 expression, often measured using the combined positive score (CPS), helps refine decisions regarding the use of immunotherapy, with higher CPS values generally associated with greater benefit. The segment emphasizes the importance of obtaining HER2 and PD-L1 results early through comprehensive molecular profiling to guide individualized treatment selection. It also addresses one of the most difficult clinical issues in gastric cancer, peritoneal metastases, which are common, frequently hard to detect with imaging, and associated with poor outcomes. These factors highlight the complexity of caring for this population despite improvements in systemic therapy.